This invention relates to a monodisperse aerosol generator and interface structure for forming an aerosol beam and introducing it into mass spectrometry apparatus. The monodisperse aerosol generator has separate utility aside and apart from the interface structure inasmuch as it may be used as a primary aerosol standard for reference purpose, as a source of injection of uniform particles to internal combustion devices, and as a source of sample solution introduction in flame and plasma atomic spectrometry (e.g., atomic absorption, atomic emission and atomic fluorescence spectroscopy). The monodisperse aerosol generator is, however, primarily intended for use as a means of solution introduction to a device acting as an interface between a liquid chromatograph and a mass spectrometer, or for direct introduction of sample solutions to the interface without the use of the liquid chromatograph. The preferred interface structure according to this invention accepts the monodisperse aerosol and desolvates it to form a solute aerosol beam which, with high purity, is introduced into a mass spectrometer.
The device is intended to provide a source of aerosol particles with a narrow particle size distribution, with a high degree of efficiency. It will be capable of producing aerosol from a wide range of liquids of varying physical properties. These liquids will include water and solutions of substances soluble in water, organic solvents and solutions of substances soluble in organic solvents. The device will produce a stable aerosol, such that the aerosol, once formed, will show little tendency to coagulate to form agglomerates of particles. The aerosol will, however, be capable of controlled evaporation for partial or complete removal of solvent. The size of the aerosol droplets will be controllable by simple means.
The device will be capable of producing a uniform and reproducible concentration of droplets in the gas stream over an extended period of time. It will also be capable of generating droplets with a wide range of selected sizes, covering a range typically of 5-200 micrometers diameter. Liquid chromatography, particularly modern high performance liquid chromatography, provides a powerful tool for the separation of complex mixtures of either organic or inorganic species into their components. It is suitable for a great range of compounds which cannot be separated using the technique of gas chromatography. Such compounds may be thermally unstable or involatile under normal gas chromatographic conditions. Many organic compounds of biological significance, and most ionic and inorganic compounds fall in this category.
Mass spectrometry is a very widely used technique for providing structural information about chemical species. Often, an unknown species may be identified with great certainty, by comparison of its mass spectrum with that of a reference mass spectrum obtained from a species of known composition. For reliable mass spectral identification of unknown species, it is generally necessary for the mass spectrometer to fulfill the following requirements: (1) mass spectra should be generated by the electron impact mode of ionization, (2) mass spectra should be generated from one species only at a time.
In a liquid chromatograph, a stream of solvent, containing a mixture of chemical species in solution, is passed at elevated pressure through a chromatographic column. The column is so designed that it separates the mixture, by differential retention on the column, into its component species. The different species then emerge from the column as distinct bands in the solvent stream, separated in time. The liquid chromatograph provides, therefore, an ideal device for the introduction into a mass spectrometer of single species, separated from initially complex mixtures.
In order for the species emerging from the column to be introduced into a mass spectrometer, partial or total removal of solvent from the dissolved species is desirable. This serves the following purposes: (1) it allows the ionization chamber of the mass spectrometer to operate at normal operating pressures (e.g. 10.sup.-5 to 10.sup.-6 torr for electron impact ionization; 1 torr for chemical ionization), (2) it allows normal ionization modes, either electron impact, chemical ionization or other to be used. Without efficient solvent removal from the species entering the ionization chamber of the mass spectrometer, hybrid and less well characterized mass spectra are produced. These types of mass spectra are generally of diminished value for unknown compound identification.
One purpose of the invention is to provide a means of introducing small samples of substances, dissolved in suitable solvent, directly into a mass spectrometer for electron impact mass spectrometry. The interface must remove the solvent and its vapor to a sufficiently low level that the electron impact mode of operation may be used. The interface may be used either as a rapid means of directly introducing samples into a mass spectrometer, or as an interface between a liquid chromatograph and a mass spectrometer. It is intended that the interface should take advantage of the inherent capabilities of each component technique, without compromising either.
Specifically, preferred goals of the invention are: (1) to allow direct, simple interfacing between the liquid chromatograph and the mass spectrometer, (2) to provide efficient species transport between the liquid chromatograph and the mass spectrometer, (3) to allow the use of all normal modes of ionization typically used for gas chromatograph/mass spectrometry, (4) to allow operation with a wide variety of solvents, (this would include solvents and solvent mixtures commonly used in normal, reversed phase and ion exchange liquid chromatograph--e.g. alcohols, nitriles, and aqueous buffers, together with mixtures of same), (5) to produce sufficiently high species enrichment in the liquid chromatography effluent, by solvent removal, that the desolvated species may be introduced directly to the ionization chamber of a normal mass spectrometer, without need for additional high pumping capacity in the mass spectrometer, (6) to allow the device to be readily incorporated into the ionization chambers of existing instruments, with minimum modification (e.g. through the direct probe inlet). (7) to be capable of reliable, routine operation. (8) to be capable of providing precise, quantitative analysis of species over at least two orders of magnitude mass range.
Previous methods for generating uniform aerosols directly from liquid streams have worked on the principle of applying a regular external disturbance to a liquid cylindrical jet. The disturbance has been applied either axially or longitudinally to the jet as it emerges from a uniform circular nozzle. The disturbance has been provided by an electromechanical device, such as a piezoelectric crystal or a loudspeaker coil, driven by a high frequency power source.
The orifices used have either been laser-drilled steel or platinum disks, or fine bore stainless steel or glass capillary tubes. In general, the smallest droplets claimed for the devices are approximately 10 micrometers for circular disk orifices and 40 micrometers for capillary devices. A typical disk device is that of Berglund and Liu.sup.1, illustrated in FIG. 1. The liquid is passed under pressure through a disk orifice, emerging as a jet which is periodically disturbed by oscillations from a piezoelectric crystal. The piezoelectric crystal is driven at a selected frequency by a radiofrequency generator. FNT .sup.1 Berglund, R. N. and Liu, B. Y. H. Env. Sci. & Technology, 7, 147 (1973). Stable and uniform aerosol production is only possible over a restricted range of liquid flow and oscillating frequency, for each particular orifice size. The initial aerosol stream is dispersed by a concentric gas jet, diluted with further air and neutralized electrically with a radioactive source, before emerging from the device.
Capillary devices are typified by that of Lindblad and Schneider.sup.2. Here liquid emerges from a stainless capillary tube, is subjected to transverse disturbances from a piezoelectric crystal under radiofrequency oscillations, and breaks into a uniform droplet stream. In general, the droplet density produced by the capillary type devices is lower than that produced by the disk devices, and so dilution gas for prevention of agglomeration is not used. FNT .sup.2 Lindblad, N. R. & Schneider, J. M., J.Sci. Instrum., 42,635 (1965).
Other devices typically used for aerosol production, and suitable for use with a wide range of solvents and solutions are pneumatic nebulizers and spinning disk nebulizers. Devices are also available which are based on ultrasonic aerosol production using focussed-beam devices.
A number of approaches to interfacing liquid chromatography with mass spectrometry have been attempted. They may be summarized under the following catagories:
Direct Liguid Introduction (DLI). With this approach, the interface between the liquid chromatograph and the mass spectrometer consists of a direct probe, having a stainless steel diaphragm at the tip. The center of the diaphragm has a small (typically 1-10 micrometer) orifice, through which part of the column effluent is sampled into the ionization chamber of the mass spectrometer, through a desolvation chamber. A liquid stream emerges from the orifice, and shatters into droplets. The droplets pass into a desolvation chamber, which is cryogenically cooled in order to trap solvent vapor, and maintain a reasonable operating pressure in the ionization chamber. The system was first described by Baldwin and McLaiferty.sup.3, and is marketed commercially by Hewlett-Packard and Ribermag. Versions have been described for both normal [1] and micro-column [2] liquid chromatography. FNT .sup.3 Baldwin, M. A. and McLafferty, F. W. Org. Mass. Spectrom.7,1353 (1973)
Mechanical Transfer Technigues. With mechanical transfer techniques, all of part of the effluent is collected onto a moving wire or belt. The liquid either flows directly onto the wire or belt, or is sprayed on as an aerosol. In either instance, a thin film of the liquid is formed, from which the solvent is evaporated in stages. The belt (or wire) passes-through several independently pumped chambers, separated by vacuum locks, before reaching the ionization chamber of the mass spectrometer. In the first chamber, the belt is usually heated radiantly, in order to evaporate solvent from the column effluent. Prior to the ion source, the belt is heated rapidly, in order to flash vaporize the species from the belt, and allow it to pass into the ion source chamber. A typical system of this type is that of McFadden.sup.4, which is available commercially from Finnigan Instruments. Another version (available commercially from VG-Organic) passes the belt directly up into the ionization chamber, in order to allow surface ionization techniques to be used. FNT .sup.4 McFadden, W. H., J. Chromatogr. Sci. 18, 97 (1980),
Aerosol Introduction Techniques. These derivatives of the DLI approach attempt to produce more efficient evaporation of solvent from the liquid chromatography column effuent, prior to its entering the ionization chamber of the mass spectrometer. The effluent emerges as a liquid jet from a small orifice, which is heated to a high temperature (typically 1000.degree. C., using an oxyhydrogen flame). The partly desolvated aersol particles are separated from the solvent vapor by means of a skimmer, before passing to the ionization chamber of the mass spectrometer. Such a device has been described by McAdams et al..sup.5, and is available commercially from Finnigan Instruments. FNT .sup.5 McAdams, M. J., Blakley, C. R. and Vestal, M. L., 26th Annual conference on Mass Spectrometry and Allied Topics, St. Louis, MO (1978).
In addition to the above, the following patents are noted in that they relate generally to interface structure for use in a combined liquid chromatography , mass spectrometry system:
______________________________________ 4,055,987 McFadden 11/1/77 4,066,411 Fine et al 1/3/78 4,112,297 Miyagi et al 9/5/78 4,281,246 White et al 7/28/81 4,298,795 Takeuchi 11/3/81 4,300,044 Iribarne et al 11/10/81 4,403,147 Melera et al 9/6/83 3,633,027 Rykage 1/4/72 3,997,298 McLafferty et al 12/14/76 4,213,326 Brodasky 7/22/80 4,391,778 Andresen et al 7/5/83 ______________________________________
No relevant prior art is known with relation to the monodisperse aerosol generator per se.